RESUMEN
Conformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is an underlying pathogenic mechanism in prion diseases. The diseases manifest as sporadic, hereditary, and acquired disorders. Etiological mechanisms driving the conversion of PrPC into PrPSc are unknown in sporadic prion diseases, while prion infection and specific mutations in the PrP gene are known to cause the conversion of PrPC into PrPSc in acquired and hereditary prion diseases, respectively. We recently reported that a neurotropic strain of influenza A virus (IAV) induced the conversion of PrPC into PrPSc as well as formation of infectious prions in mouse neuroblastoma cells after infection, suggesting the causative role of the neuronal infection of IAV in sporadic prion diseases. Here, we discuss the conversion mechanism of PrPC into PrPSc in different types of prion diseases, by presenting our findings of the IAV infection-induced conversion of PrPC into PrPSc and by reviewing the so far reported transgenic animal models of hereditary prion diseases and the reverse genetic studies, which have revealed the structure-function relationship for PrPC to convert into PrPSc after prion infection.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/genética , Enfermedad de Gerstmann-Straussler-Scheinker/genética , Gripe Humana/genética , Insomnio Familiar Fatal/genética , Proteínas PrPC/genética , Proteínas PrPSc/genética , Proteínas Priónicas/genética , Animales , Línea Celular Tumoral , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Síndrome de Creutzfeldt-Jakob/virología , Enfermedad de Gerstmann-Straussler-Scheinker/metabolismo , Enfermedad de Gerstmann-Straussler-Scheinker/patología , Enfermedad de Gerstmann-Straussler-Scheinker/virología , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/crecimiento & desarrollo , Virus de la Influenza A/patogenicidad , Gripe Humana/metabolismo , Gripe Humana/patología , Gripe Humana/virología , Insomnio Familiar Fatal/metabolismo , Insomnio Familiar Fatal/patología , Insomnio Familiar Fatal/virología , Ratones , Ratones Transgénicos , Mutación , Neuronas/metabolismo , Neuronas/patología , Neuronas/virología , Proteínas PrPC/química , Proteínas PrPC/metabolismo , Proteínas PrPSc/química , Proteínas PrPSc/metabolismo , Proteínas Priónicas/química , Proteínas Priónicas/metabolismo , Conformación Proteica , Genética Inversa/métodosRESUMEN
The following questions are discussed in this paper: (1) Can the bovine prion protein PrpRES infect a man? (2) What is the route of PrPRES infection? (3) In what condition the PrPRES may infect animals, (4) What are the normal functions of PrPc at the surface of neurons and neuroglia cells, (5) What is the structure of the prion protein, (6) What is possible mechanism of the PrPRES destroying neurons. Finally, the two possible mechanisms of the PrPRES to affect central nervous system are analysed. One is to destroy the normal function of the PrPC, the other is to raise the sensibility of the neuron to the free radical and increase the content of the oxygen radical.
Asunto(s)
Priones/fisiología , Priones/patogenicidad , Animales , Bovinos , Síndrome de Creutzfeldt-Jakob/virología , Encefalopatía Espongiforme Bovina/transmisión , Encefalopatía Espongiforme Bovina/virología , Enfermedad de Gerstmann-Straussler-Scheinker/virología , HumanosRESUMEN
On the basis of clinical picture of the disease, data of CT, MRT, psychological study, original laboratory investigation aimed at indication of changes in transposed neuroglia cells induced by the causal agent of subacute spongious transmissible encephalopathies, the diagnosis of patient K., 49 years old, was considered to be: syndrome of Gertsmann-Sträussler [correction of Herstmann Streussler]. Duration of the disease was 2 years. The case was sporadic. The history of the problem, modern views on etiology, pathogenesis of preventive measures are presented.
